Abernethy N J, Hagan C, Tan P L, Watson J D
Genesis Research and Development Corporation Limited, Auckland, New Zealand.
Immunol Cell Biol. 2000 Dec;78(6):596-602. doi: 10.1046/j.1440-1711.2000.00945.x.
T-cell activation is considered to be an important element in the pathogenesis of psoriasis, a human skin disease characterized by keratinocyte hyperproliferation, altered keratinocyte differentiation and inflammation of the dermis and epidermis. Mice homozygous for the flaky skin (fsn) mutation develop a skin disorder that has histopathological and biochemical features resembling some forms of psoriasis. It has been reported recently that peripheral lymph nodes (PLN) in fsn/fsn mice exhibit various abnormalities in T-cell development suggestive of dysregulated T- and B-cell activation. In the present study, the expression of the inducible T-cell activation antigens CD69 and IL-2 receptor alpha chain (CD25) on PLN cells from fsn/fsn mice and their phenotypically normal littermates is examined. Expression of CD69 was significantly increased on PLN cells in fsn/fsn mice (mean +/- SD, 49.9 +/- 14.7% of cells) compared with control mice (14.6 +/- 4.2%). Analysis of CD4+ and CD8+ T cell subsets revealed that expression of CD69 in fsn/fsn PLN was significantly biased toward CD8+ cells. Although expression of CD25 was preferentially associated with CD4+ rather than CD8+ cells in both fsn/fsn and control PLN, with most CD4+ CD25+ cells being CD25hi, the proportion of CD4+ cells expressing CD25 was higher in fsn/fsn than control PLN. In contrast, CD25 was expressed by 2-3% of CD8+ PLN cells in both fsn/fsn and control mice and CD25hi cells accounted for < 1% of CD8+ cells in fsn/fsn PLN. The paucity of CD25 on CD8+ cells in fsn/fsn PLN did not appear to be due to a defect in the ability of these cells to upregulate CD25, because T cell receptor stimulation in vitro induced high expression of CD25 on both CD4+ and CD8+ cells. A striking and consistent finding was that most CD8+ cells in fsn/fsn PLN expressed high levels of IL-2R beta chain (CD122). In contrast, CD122 was expressed at low levels on CD8+ cells in control mice. Analysis of PLN cells from newborn fsn/fsn mice revealed that the high expression of CD122 on CD8+ cells was established by 2 weeks of age, prior to the appearance of clinical skin disease. These data indicate that large numbers of T cells in fsn/fsn mice are activated and reinforce the view that fsn is an important regulator of lymphocyte development and function. The relationship between T-cell activation and flaky skin disease in these mice remains to be established.
T细胞活化被认为是银屑病发病机制中的一个重要因素，银屑病是一种人类皮肤疾病，其特征为角质形成细胞过度增殖、角质形成细胞分化改变以及真皮和表皮炎症。皮肤片状脱落（fsn）突变的纯合小鼠会出现一种皮肤疾病，其组织病理学和生化特征类似于某些形式的银屑病。最近有报道称，fsn/fsn小鼠的外周淋巴结（PLN）在T细胞发育方面表现出各种异常，提示T细胞和B细胞活化失调。在本研究中，检测了fsn/fsn小鼠及其表型正常的同窝小鼠PLN细胞上诱导型T细胞活化抗原CD69和白细胞介素2受体α链（CD25）的表达。与对照小鼠（14.6±4.2%）相比，fsn/fsn小鼠PLN细胞上CD69的表达显著增加（平均值±标准差，49.9±14.7%的细胞）。对CD4+和CD8+T细胞亚群的分析显示，fsn/fsn PLN中CD69的表达明显偏向于CD8+细胞。虽然在fsn/fsn和对照PLN中，CD25的表达都优先与CD4+而非CD8+细胞相关，大多数CD4+CD25+细胞为CD25高表达，但fsn/fsn中表达CD25的CD4+细胞比例高于对照PLN。相比之下，fsn/fsn和对照小鼠中CD8+PLN细胞中分别有2 - 3%表达CD25，fsn/fsn PLN中CD25高表达细胞占CD8+细胞的比例不到1%。fsn/fsn PLN中CD8+细胞上CD25的缺乏似乎不是由于这些细胞上调CD25的能力缺陷，因为体外T细胞受体刺激可诱导CD4+和CD8+细胞上CD25的高表达。一个显著且一致的发现是，fsn/fsn PLN中的大多数CD8+细胞表达高水平的白细胞介素2受体β链（CD122）。相比之下，对照小鼠CD8+细胞上CD122的表达水平较低。对新生fsn/fsn小鼠PLN细胞的分析显示，CD8+细胞上CD122的高表达在2周龄时就已确立，早于临床皮肤疾病的出现。这些数据表明，fsn/fsn小鼠中有大量T细胞被激活，并强化了fsn是淋巴细胞发育和功能重要调节因子的观点。这些小鼠中T细胞活化与皮肤片状脱落疾病之间的关系仍有待确定。
